Ras/MEK but not p38 signaling mediates NT-3-induced neurite extension from spiral ganglion neurons

被引:46
作者
Aletsee, C
Beros, A
Mullen, L
Palacios, S
Pak, K
Dazert, S
Ryan, AF
机构
[1] Univ Calif San Diego, Sch Med, Dept Surg Otolaryngol & Neurosci, La Jolla, CA 92093 USA
[2] VA Med Ctr, La Jolla, CA 92093 USA
[3] Univ Wurzburg, Dept Otolaryngol Head & Neck Surg, D-97080 Wurzburg, Germany
来源
JARO-JOURNAL OF THE ASSOCIATION FOR RESEARCH IN OTOLARYNGOLOGY | 2001年 / 2卷 / 04期
关键词
MEK; Ras; p38; spiral ganglion; development; rat;
D O I
10.1007/s10162001000086
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Neurotrophin (NT)-3 is expressed in the neuronal target tissue of the developing rat cochlea and has been shown to promote the survival and neurite outgrowth of spiral ganglion (SG) neurons, suggesting a role for this protein during the innervation of the organ of Corti. In other neurons, NT-3 can mediate neuritogenesis and survival via a number of intracellular signal pathways. To date, the intracellular transduction pathways involved in the mediation of NT-3 effects have not been investigated in SG neurons. To determine whether the activities of NT-3 on SG neurons are dependent on the activation of mitogen-activated protein kinase kinases (MEK)/extracellular-signal-regulated kinases (ERK), Ras, and/or p38, SG explants from postnatal-day 4 rats were cultured with NT-3 and increasing concentrations of the MEK inhibitor U0126, the Ras farnesyl-transferase inhibitor (FTI)-277, and the p38 inhibitor SB203580. After fixation and immunocytochemical labeling, neurite growth was evaluated. A dose-dependent decrease of the effects of NT-3 on length and number of processes was observed in the U0126- and FTI-277-treated SG neurons. In contrast, SB203580 had no significant effect on NT-3-mediated stimulation of neurite growth, in terms of either number or length. The results suggest that NT-3 effects on SG neurons are mediated primarily by the Ras/MEK/ERK signaling pathway.
引用
收藏
页码:377 / 387
页数:11
相关论文
共 54 条
[1]   Neurotrophic effect of basic fibroblast growth factor is mediated by the p42/p44 mitogen-activated protein kinase cascade in cultured rat cortical neurons [J].
Abe, K ;
Saito, H .
DEVELOPMENTAL BRAIN RESEARCH, 2000, 122 (01) :81-85
[2]   The mitogen-activated protein kinase cascade mediates neurotrophic effect of epidermal growth factor in cultured rat hippocampal neurons [J].
Abe, K ;
Saito, H .
NEUROSCIENCE LETTERS, 2000, 282 (1-2) :89-92
[3]   A rapid method for semi-quantitative analysis of neurite outgrowth from chick DRG explants using image analysis [J].
Bilsland, J ;
Rigby, M ;
Young, L ;
Harper, S .
JOURNAL OF NEUROSCIENCE METHODS, 1999, 92 (1-2) :75-85
[4]  
Blanquet PR, 2000, NEUROSCIENCE, V95, P705
[5]   ERKS - A FAMILY OF PROTEIN-SERINE THREONINE KINASES THAT ARE ACTIVATED AND TYROSINE PHOSPHORYLATED IN RESPONSE TO INSULIN AND NGF [J].
BOULTON, TG ;
NYE, SH ;
ROBBINS, DJ ;
IP, NY ;
RADZIEJEWSKA, E ;
MORGENBESSER, SD ;
DEPINHO, RA ;
PANAYOTATOS, N ;
COBB, MH ;
YANCOPOULOS, GD .
CELL, 1991, 65 (04) :663-675
[6]   MEK inhibitors block BDNF-dependent and -independent expression of GABAA receptor subunit mRNAs in cultured mouse cerebellar granule neurons [J].
Bulleit, RF ;
Hsieh, T .
DEVELOPMENTAL BRAIN RESEARCH, 2000, 119 (01) :1-10
[7]   Protein prenyltransferases [J].
Casey, PJ ;
Seabra, MC .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271 (10) :5289-5292
[8]   NEUROTROPHIN RECEPTORS - A WINDOW INTO NEURONAL DIFFERENTIATION [J].
CHAO, MV .
NEURON, 1992, 9 (04) :583-593
[9]   PURIFICATION OF A MURINE PROTEIN-TYROSINE THREONINE KINASE THAT PHOSPHORYLATES AND ACTIVATES THE ERK-1 GENE-PRODUCT - RELATIONSHIP TO THE FISSION YEAST BYR1 GENE-PRODUCT [J].
CREWS, CM ;
ERIKSON, RL .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1992, 89 (17) :8205-8209
[10]  
Dazert S, 1998, J CELL PHYSIOL, V177, P123, DOI 10.1002/(SICI)1097-4652(199810)177:1<123::AID-JCP13>3.0.CO